ONCOGENE MTDH MEDIATES EMT TO PROMOTE THE INVASION OF BLADDER CANCER CELLS THROUGH WNT/Β CATENIN SIGNAL PATHWAY

Jun Zheng¹, Shuai Yuan^{2, *}, Li Zhu¹, Shijian Li¹, Gaoliang Chen¹

¹Department of Urology Surgery, Chongqing People's General Hospital, Chongqing, PR China - ²Department of Urology, Shanxi Bethune Hospital, Shanxi Academy Of Medical Sciences, Taiyuan, PR China

Objective: To analyse the effect of oncogene Metaherin (MTDH) on mediating epithelial-mesenchymal transition (EMT) to promote the invasion of bladder cancer cells through the Wnt/β catenin signal pathway. 

Methods: Cancer tissues and normal adjacent tissues were taken from 114 patients with bladder cancer who underwent surgery in our hospital from March 2016 to May 2018. The expression of MTDH in the cancer tissue and normal adjacent tissue were determined by immunohistochemistry. The human bladder cancer cell line 5637 cells were infected with lentivirus to prepare MTDH over-expressing cell lines (MTDH over-expressing group). At the same time, non-infected cells were set as normal groups. CCK-8 method was used to detect cell proliferation. Apoptosis was detected by flow cytometry. The effect of MTDH overexpression on the migration ability of 5637 cells was detected by a scratch test. The effect of MTDH overexpression on the invasion ability of 5637 cells was tested by a Transwell cell invasion experiment. The effect of 5637 cells with MTDH overexpression on the expression of E cadherin protein, β catenin protein and c Myc protein was detected by Western blot. 

Results: The expression level of MTDH in the bladder cancer tissue was significantly lower than that in the normal adjacent tissues. With time prolonged, the cell proliferation ability of the MTDH overexpression group and the normal group showed an increasing trend. From 12h, the cell proliferation ability of the MTDH overexpression group was significantly higher than that of the normal group (p<0.05). Compared with the normal group, the apoptosis of the MTDH overexpression group was significantly reduced (p<0.05). The migration ability of 5637 cells in the MTDH overexpression group was significantly enhanced compared with the normal group (p<0.05). Compared with the normal group, the invasion ability of 5637 cells in the MTDH overexpression group was significantly increased (p<0.05). The expression level of E cadherin protein in 5637 cells was significantly lower, but the expression levels of total β catenin protein and c Myc protein were significantly higher in the MTDH overexpression group than those in the normal group (p<0.05). 

Conclusion: Oncogene MTDH overexpression can activate Wnt/β catenin signal pathway, enhance the invasion ability of bladder cancer cells and promote EMT development.